High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni.
In a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-gamma, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-gamma and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-gamma and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p < 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p < 0.001), sTNFR-II, (p < 0.0001), and sICAM-1 (p < 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.
Mwatha
J K
JK
Kenya Medical Research Institute, Division of Vector Borne Diseases, Nairobi.
Kimani
G
G
Kamau
T
T
Mbugua
G G
GG
Ouma
J H
JH
Mumo
J
J
Fulford
A J
AJ
Jones
F M
FM
Butterworth
A E
AE
Roberts
M B
MB
Dunne
D W
DW
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood*; D015848:Interleukin-5 / Q000097:blood*; D008109:Liver Diseases, Parasitic / Q000276:immunology* / Q000473:pathology; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D013158:Splenic Diseases / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D016207:Cytokines; D015848:Interleukin-5; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma